2A65: Crystal Structure Of Leutaa, A Bacterial Homolog Of Na+/cl--dependent Neurotransmitter Transporters

Na+/Cl--dependent transporters terminate synaptic transmission by using electrochemical gradients to drive the uptake of neurotransmitters, including the biogenic amines, from the synapse to the cytoplasm of neurons and glia. These transporters are the targets of therapeutic and illicit compounds, and their dysfunction has been implicated in multiple diseases of the nervous system. Here we present the crystal structure of a bacterial homologue of these transporters from Aquifex aeolicus, in complex with its substrate, leucine, and two sodium ions. The protein core consists of the first ten of twelve transmembrane segments, with segments 1-5 related to 6-10 by a pseudo-two-fold axis in the membrane plane. Leucine and the sodium ions are bound within the protein core, halfway across the membrane bilayer, in an occluded site devoid of water. The leucine and ion binding sites are defined by partially unwound transmembrane helices, with main-chain atoms and helix dipoles having key roles in substrate and ion binding. The structure reveals the architecture of this important class of transporter, illuminates the determinants of substrate binding and ion selectivity, and defines the external and internal gates.
PDB ID: 2A65Download
MMDB ID: 34395
PDB Deposition Date: 2005/7/1
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.65  Å
Source Organism:
Similar Structures:
Biological Unit for 2A65: monomeric; determined by author and by software (PISA)
Molecular Components in 2A65
Label Count Molecule
Protein (1 molecule)
Na(+):neurotransmitter Symporter (Snf Family)
Molecule annotation
Chemicals (9 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB